TY - JOUR
T1 - Inhibition of pancreatic cancer cell growth and induction of apoptosis with novel therapies directed against protein kinase A
AU - Farrow, Buckminster
AU - Rychahou, Piotr
AU - Murillo, Carlos
AU - O'Connor, Kathleen L.
AU - Iwamura, Takeshi
AU - Evers, B. Mark
N1 - Funding Information:
Supported by grants from the National Institutes of Health (RO1 DK48498, PO1 DK35608, and T32 DK07639).
PY - 2003/8/1
Y1 - 2003/8/1
N2 - Background. Pancreatic cancer is the most lethal abdominal malignancy. Expression of the RIα subunit of protein kinase A (PKA) has been associated with neoplastic transformation and mitogenic signaling. The effect of PKA inhibition on pancreatic cancer cell growth and apoptosis is unknown. In pancreatic cancer cells, we sought to determine (1) whether inhibition of PKA can inhibit growth or induce apoptosis, and (2) whether growth can be inhibited by silencing' of RIα expression. Methods. Human pancreatic cancer cells (PANC-1, MIA PaCa-2, and SUIT-2) were treated with inhibitors of PKA (H89 or PKI) and cell growth, kinase activity, and induction of apoptosis measured. Small inhibitory RNA (siRNA) directed against the RIα subunit was synthesized and transfected into PANC-1 cells. Results. H89 decreased PKA activity and inhibited pancreatic cancer cell growth. Apoptosis was also induced by H89 in PANC-1 and MIA PaCa-2 cells. PANC-1 cells express high levels of the RIα subunit; transfection of siRNA decreased RIα protein expression and inhibited growth. Conclusions. Inhibition of PKA in pancreatic cancer cells induces growth arrest and apoptosis; similar effects are noted in cells with siRNA used to block RIα expression. Inhibition of PKA may represent a novel therapeutic strategy for the adjuvant treatment of pancreatic cancer.
AB - Background. Pancreatic cancer is the most lethal abdominal malignancy. Expression of the RIα subunit of protein kinase A (PKA) has been associated with neoplastic transformation and mitogenic signaling. The effect of PKA inhibition on pancreatic cancer cell growth and apoptosis is unknown. In pancreatic cancer cells, we sought to determine (1) whether inhibition of PKA can inhibit growth or induce apoptosis, and (2) whether growth can be inhibited by silencing' of RIα expression. Methods. Human pancreatic cancer cells (PANC-1, MIA PaCa-2, and SUIT-2) were treated with inhibitors of PKA (H89 or PKI) and cell growth, kinase activity, and induction of apoptosis measured. Small inhibitory RNA (siRNA) directed against the RIα subunit was synthesized and transfected into PANC-1 cells. Results. H89 decreased PKA activity and inhibited pancreatic cancer cell growth. Apoptosis was also induced by H89 in PANC-1 and MIA PaCa-2 cells. PANC-1 cells express high levels of the RIα subunit; transfection of siRNA decreased RIα protein expression and inhibited growth. Conclusions. Inhibition of PKA in pancreatic cancer cells induces growth arrest and apoptosis; similar effects are noted in cells with siRNA used to block RIα expression. Inhibition of PKA may represent a novel therapeutic strategy for the adjuvant treatment of pancreatic cancer.
UR - http://www.scopus.com/inward/record.url?scp=0042328100&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0042328100&partnerID=8YFLogxK
U2 - 10.1067/msy.2003.220
DO - 10.1067/msy.2003.220
M3 - Article
C2 - 12947318
AN - SCOPUS:0042328100
VL - 134
SP - 197
EP - 205
IS - 2
ER -
